Process for improved opioid synthesis

Abstract

Compounds and compositions for use as starting materials or intermediate materials in the preparation of opioids including, e.g., oxymorphone base and/or an oxymorphone salt; processes for preparing these compounds and compositions; uses of these compounds and compositions in the preparation of APIs and pharmaceutical dosage forms; and uses of said APIs and pharmaceutical dosage forms in the treatment of medical conditions.

1 - 134 . (canceled) 
     
     
         135 . A compound, which is an isolated compound having the formula V or a solvate thereof 
       
         
           
           
               
               
           
         
         wherein R 1  is —H, aralkyl, —(C 1 -C 6 )alkenyl, —SiR 3   3 , —(C 3 -C 7 )cycloalkyl, —(C 1 -C 7 )alkyl-(C 3 -C 7 )cycloalkyl, —(C 3 -C 7 )cycloalkenyl, —(C 1 -C 7 )alkyl-(C 3 -C 7 )cycloalkenyl, —CR 4   2 —O—(C 1 -C 6 )alkyl, —C(halo) 3 , —CH 2 (halo), —CH(halo) 2 , —SO 2 R 5 , or an O-protecting group, 
         R 2  is —H, —CH 3 , —(C 2 -C 7 )alkyl, —(C 2 -C 4 )alkenyl, benzyl, —(C 1 -C 7 )alkyl-(C 3 -C 7 )cycloalkyl, —CN, or an N-protecting group, and 
         X n−  is S 4   2− , and n is 2. 
       
     
     
         136 - 138 . (canceled) 
     
     
         139 . The compound having the formula V of  claim 135 , wherein R 1  is —H. 
     
     
         140 . The compound having the formula V of  claim 135 , wherein R 2  is —CH 3 . 
     
     
         141 . The compound having the formula V of  claim 135 , wherein R 2  is —H. 
     
     
         142 . The compound having the formula V of  claim 135 , which is 
       
         
           
           
               
               
           
         
         or a hydrate thereof. 
       
     
     
         143 . The compound having the formula V of  claim 135 , which is 
       
         
           
           
               
               
           
         
         or a hydrate thereof. 
       
     
     
         144 . The compound having the formula V of  claim 135 , which is a hydrate of isolated 14-hydroxymorphinone sulfate having formula 
       
         
           
           
               
               
           
         
       
     
     
         145 . The compound having the formula V of  claim 135 , which is the hydrate of the compound of formula V. 
     
     
         146 . The compound having the formula V of  claim 145 , wherein the hydrate is a hydrate containing from 0.1 to 6.9 water molecules per molecule of the compound of formula V. 
     
     
         147 . The compound of  claim 145 , which is a monohydrate, dihydrate, trihydrate, tetrahydrate, pentahydrate, or hexahydrate. 
     
     
         148 . The compound of  claim 147 , which is a monohydrate or a pentahydrate. 
     
     
         149 - 152 . (canceled) 
     
     
         153 . A composition comprising the compound of formula V according to  claim 135 . 
     
     
         154 . The composition of  claim 153 , which additionally comprises a compound of formula III 
       
         
           
           
               
               
           
         
         wherein R 1  is —H, aralkyl, —(C 2 -C 6 )alkenyl, —SiR 3   3 , —(C 3 -C 7 )cycloalkyl, —(C 7 -C 7 )alkyl-(C 3 -C 7 )cycloalkyl, —(C 3 -C 7 )cycloalkenyl, —(C 1 -C 7 )alkyl-(C 3 -C 7 )cycloalkenyl, —CR 4   2 —O—(C 1 -C 6 )alkyl, —C(halo) 3 , —CH 2 (halo), —CH(halo) 2 , —SO 2 R 5 , or an O-protecting group, and R 2  is —H, —CH 3 —(C 2 -C 7 )alkyl, —(C 2 -C 4 )alkenyl, benzyl, —(C 1 -C 7 )alkyl-(C 3 -C 7 )cycloalkyl, —CN, or an N-protecting group, 
         or a salt or solvate thereof. 
       
     
     
         155 . The composition of  claim 154 , wherein the amount of the compound of formula III in the composition is less than about 2500 ppm, less than about 2250 ppm, less than about 2000 ppm, less than about 1750 ppm, less than about 1500 ppm, or less than about 1250 ppm of the compound of formula V (HPLC peak area ratio). 
     
     
         156 . The composition of  claim 154 , wherein the amount of the compound of formula III in the composition is less than about 1000 ppm, less than about 750 ppm, less than about 500 ppm, less than about 400 ppm, less than about 300, less than about 250 ppm, less than about 200 ppm, or less than about 150 ppm of the compound of formula V (HPLC peak area ratio). 
     
     
         157 . The composition of  claim 154 , wherein the amount of the compound of formula III in the composition is less than about 100 ppm, less than about 90 ppm, less than about 80 ppm, less than about 70 ppm, less than about 60 ppm, less than about 50 ppm, less than about 40 ppm, less than about 30 ppm, or less than about 20 ppm of the compound of formula V (HPLC peak area ratio). 
     
     
         158 . The composition of  claim 154 , wherein the amount of the compound of formula III in the composition is less than about 10 ppm, less than about 8 ppm, less than about 6 ppm, less than about 4 ppm, or less than about 2 ppm of the compound of formula V (HPLC peak area ratio). 
     
     
         159 . The composition of  claim 154 , wherein the amount of the compound of formula III in the composition is less than about 1 ppm, less than about 0.8 ppm, less than about 0.6 ppm, less than about 0.4 ppm, less than about 0.3 ppm, less than about 0.2 ppm, or less than about 0.1 ppm of the compound of formula V (HPLC peak area ratio). 
     
     
         160 - 242 . (canceled)